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. 2009 Aug;26(8):1353-9.
doi: 10.1089/neu.2008.0858.

Traumatic brain injury and intestinal dysfunction: uncovering the neuro-enteric axis

Vishal Bansal  1 , Todd Costantini, Lauren Kroll, Carrie Peterson, William Loomis, Brian Eliceiri, Andrew Baird, Paul Wolf, Raul Coimbra
Affiliations

Traumatic brain injury and intestinal dysfunction: uncovering the neuro-enteric axis

Vishal Bansal et al. J Neurotrauma. 2009 Aug.

Abstract

Traumatic brain injury (TBI) can lead to several physiologic complications including gastrointestinal dysfunction. Specifically, TBI can induce an increase in intestinal permeability, which may lead to bacterial translocation, sepsis, and eventually multi-system organ failure. However, the exact mechanism of increased intestinal permeability following TBI is unknown. We hypothesized that expression of tight junction protein ZO-1 and occludin, responsible for intestinal architectural and functional integrity, will decrease following TBI and increase intestinal permeability. BALB/c mice underwent a weight drop TBI model following anesthesia. Brain injury was confirmed by a neurologic assessment and gross brain pathology. Six hours following injury, FITC-dextran (25 mg 4.4 kDa FITC-dextran) was injected into the intact lumen of the isolated ileum. Intestinal permeability was measured in plasma 30 min following injection, by using spectrophotometry to determine plasma FITC-dextran concentrations. Whole ileum extracts were used to measure expression of tight junction proteins ZO-1 and occludin by Western blot. TBI caused a significant increase in intestinal permeability (110.0 microg/mL +/-22.2) compared to sham animals (29.4 microg/mL +/- 9.7) 6 h after injury (p = 0.016). Expression of ZO-1 was decreased by 49% relative to sham animals (p < 0.02), whereas expression of occludin was decreased by 73% relative to sham animals (p < 0.001). An increase in intestinal permeability corresponds with decreased expression of tight junction proteins ZO-1 and occludin following TBI. Expression of intestinal tight junction proteins may be an important factor in gastrointestinal dysfunction following brain injury.

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Figures

FIG. 1.
FIG. 1.
Representative brain tissue from mice following the weight drop TBI model (A) and sham (B). The TBI brain shows a focal hemorrhagic contusion.
FIG. 2.
FIG. 2.
Intestinal permeability as determined by serum FITC-dextran (25 mg 4.4-kDa FITC-dextran in 200 μL PBS) injected into the lumen of the isolated ileum in both sham (n = 4) and TBI mice (n = 4). TBI caused a significant increase in intestinal permeability (110.0 ± 22.2 μg/mL) compared to sham (29.4 ± 9.7 μg/mL) after 6 h (p = 0.016).
FIG. 3.
FIG. 3.
Representative H&E staining and microscopy (60×) from the terminal ileum harvested 6 h following both TBI and sham mice. Sham animals (A) had normal-appearing villi with consistent villous height. The histologic appearance of intestinal specimens from TBI animals (B) were notable for marked blunting of intestinal villi.
FIG. 4.
FIG. 4.
Expression of ZO-1 was measured in intestinal protein extracts 6 h following TBI or sham injury by Western immunoblotting (n = 4 animals in each group). Intestinal ZO-1 expression was decreased by 49% in TBI animals compared to sham animals (p < 0.02). The Western blots of all four animals from each group are shown with β-actin (S, sham; T, TBI).
FIG. 5.
FIG. 5.
Expression of occludin was measured in intestinal protein extracts 6 h following TBI or sham injury by Western immunoblotting (n = 4 animals in each group). Intestinal occludin expression was decreased by 73% in TBI animals compared to sham animals (p < 0.001). The Western blots of all four animals from each group are shown with β-actin (S, sham; T, TBI).
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References

    1. Anderson J.M. Van Itallie C.M. Tight junctions and the molecular basis for regulation of paracellular permeability. Am. J. Physiol. 1995;269:G467–G475. - PubMed
    1. Baguley I.J. Heriseanu R.E. Cameron I.D. Nott M.T. Slewa-Younan S. A critical review of the pathophysiology of dysautonomia following traumatic brain injury. Neurocrit. Care. 2008;8:293–300. - PubMed
    1. Bush T.G. Savidge T.C. Freeman T.C. Cox H.J. Campbell E.A. Mucke L. Johnson M.H. Sofroniew M.V. Fulminant jejuno-ileitis following ablation of enteric glia in adult transgenic mice. Cell. 1998;93:189–201. - PubMed
    1. Chen G. Shi J. Jin W. Wang L. Xie W. Sun J. Hang C. Progesterone administration modulates TLRs/NF-kappaB signaling pathway in rat brain after cortical contusion. Ann. Clin. Lab. Sci. 2008b;38:65–74. - PubMed
    1. Chen G. Shi J. Qi M. Yin H. Hang C. Glutamine decreases intestinal nuclear factor kappa B activity and pro-inflammatory cytokine expression after traumatic brain injury in rats. Inflamm. Res. 2008a;57:57–64. - PubMed

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